The dsRNA isolated from Escherichia coli infected with the MS2 bacteriophage induces the production of interferons.

Viral infections pose a significant threat to public health, and the production of interferons represents one of the most critical antiviral innate immune responses of the host. Consequently, the screening and identification of compounds or reagents that induce interferon production are of paramount importance. This study commenced with the cultivation of host bacterium 15,597, followed by the infection of Escherichia coli with the MS2 bacteriophage. Utilizing the J2 capture technique, a class of dsRNA mixtures (MS2+15,597) was isolated from the E. coli infected with the MS2 bacteriophage. Subsequent investigations were conducted on the immunostimulatory activity of the MS2+15,597 mixture. The results indicated that the dsRNA mixtures (MS2+15,597) extracted from E. coli infected with the MS2 bacteriophage possess the capability to activate innate immunity, thereby inducing the production of interferon-ß. These dsRNA mixtures can activate the RIG-I and TLR3 pattern recognition receptors, stimulating the expression of interferon stimulatory factors 3/7, which in turn triggers the NF-κB signaling pathway, culminating in the cellular production of interferon-ß to achieve antiviral effects. This study offers novel insights and strategies for the development of broad-spectrum antiviral drugs, potentially providing new modalities for future antiviral therapies.

Nickel Phosphonate MOF Derived N-Doped Carbon-Coated Phosphorus-Vacancies-Rich Ni2 P Particles as Efficient Bifunctional Oxygen Electrocatalyst.

The design of non-noble metal bifunctional electrocatalysts with outstanding performance and remarkable stability for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is one of the most essential issues to the realization of rechargeable zinc-air battery, and transition metal phosphides (TMPs) have emerged as robust candidates for oxygen electrocatalysts. Herein, N-doped carbon-coated phosphorus-vacancies-rich Ni2 P particles (Vp -Ni2 P@NC) is proposed via simple carbonization and following Ar plasma treatment from a single nickel phosphonate metal-organic framework (MOF) without extra phosphine and nitrogen sources. The facile and rapid plasma treatment can achieve phosphorus vacancies which could modulate the electronic structure to enhance the inherent active and electrical conductivity. Meanwhile, the pyridine-N and graphitized-N produced during calcination also could provide more active sites and increase the electrical conductivity. The resultant Vp -Ni2 P@NC catalyst shows excellent bifunctional electrocatalytic activity (OER/ORR) based on synergistic effect of introducing P vacancies into Ni2 P and N-doped carbon. Vp -Ni2 P@NC catalyst shows more advantageous ΔE value (0.70 V) compared to Pt/C+RuO2 (0.73 V) and most reported catalysts. Additionally, the zinc-air bbatterie (ZAB) employing Vp -Ni2 P@NC as air cathode shows excellent performance. The maximum power density of 203.48 mW cm-2 , the cycling stability of more than 150 h at 10 mA cm-2 .

Smartphone-based colorimetric sensor array using gold nanoparticles for rapid distinguishment of multiple pesticides in real samples.

A simple, sensitive method for pesticide distinguishment based on a colorimetric sensor array using diverse gold nanoparticles (AuNPs) at room temperature is presented in this study. Acetylcholinesterase (AChE) hydrolysis ability was influenced by different pesticides and produced different concentrations of thiocholine by hydrolyzing acetylthiocholine iodide (ATCh). Thiocholine could be easily linked to the AuNPs through an Au - S covalent bond, and AuNPs underwent aggregation, resulting in a visible color change due to alteration of surface plasmon resonance properties. Based on these results, we successfully distinguished eight pesticides (glyphosate, thiram, imidacloprid, tribenuron methyl, nicosulfuron, thifensulfuron methyl, dichlorprop, and fenoprop) utilizing five different AuNPs by colorimetric assay. The limit of detection (LOD) of this visual method for all pesticides was less than 1.5 × 10-7 M, which was more sensitive than the U.S. Environmental Protection Agency regulations specify (1.18 âˆ¼ 3.91 × 10-6 M). This method was further improved by combining a portable smartphone device with a color picking application using (color name AR) and RGB (red, green, blue) values. The method was successfully applied to pesticide residue distinguishment in real samples by linear discriminant analysis (LDA).

Targeted screening of genetic associations with COVID-19 susceptibility and severity.

The COVID-19 pandemic has resulted in great morbidity and mortality worldwide and human genetic factors have been implicated in the susceptibility and severity of COVID-19. However, few replicate researches have been performed, and studies on associated genes mainly focused on genic regions while regulatory regions were a lack of in-depth dissection. Here, based on previously reported associated variants and genes, we designed a capture panel covering 1,238 candidate variants and 25 regulatory regions of 19 candidate genes and targeted-sequenced 96 mild and 145 severe COVID-19 patients. Genetic association analysis was conducted between mild and severe COVID-19 patients, between all COVID-19 patients and general population, or between severe COVID-19 patients and general population. A total of 49 variants were confirmed to be associated with susceptibility or severity of COVID-19 (p < 0.05), corresponding to 18 independent loci. Specifically, rs1799964 in the promoter of inflammation-related gene TNF, rs9975538 in the intron of interferon receptor gene IFNAR2, rs429358 in the exon of APOE, rs1886814 in the intron of FOXP4-AS1 and a list of variants in the widely reported 3p21.31 and ABO gene were confirmed. It is worth noting that, for the confirmed variants, the phenotypes of the cases and controls were highly consistent between our study and previous reports, and the confirmed variants identified between mild and severe patients were quite different from those identified between patients and general population, suggesting the genetic basis of susceptibility and severity of SARS-CoV-2 infection might be quite different. Moreover, we newly identified 67 significant associated variants in the 12 regulatory regions of 11 candidate genes (p < 0.05). Further annotation by RegulomeDB database and GTEx eQTL data filtered out two variants (rs11246060 and rs28655829) in the enhancer of broad-spectrum antiviral gene IFITM3 that might affect disease severity by regulating the gene expression. Collectively, we confirmed a list of previously reported variants and identified novel regulatory variants associated with susceptibility and severity of COVID-19, which might provide biological and clinical insights into COVID-19 pathogenesis and treatment.

Pilot genome-wide association study of antibody response to inactivated SARS-CoV-2 vaccines.

Vaccines are a key weapon against the COVID-19 pandemic caused by SARS-CoV-2. However, there are inter-individual differences in immune response to SARS-CoV-2 vaccines and genetic contributions to these differences have barely been investigated. Here, we performed genome-wide association study (GWAS) of antibody levels in 168 inactivated SARS-CoV-2 vaccine recipients. A total of 177 SNPs, corresponding to 41 independent loci, were identified to be associated with IgG, total antibodies or neutral antibodies. Specifically, the rs4543780, the intronic variant of FAM89A gene, was associated with total antibodies level and was annotated as a potential regulatory variant affecting gene expression of FAM89A, a biomarker differentiating bacterial from viral infections in febrile children. These findings might advance our knowledge of the molecular mechanisms driving immunity to SARS-CoV-2 vaccine.

The role of ZNF143 overexpression in rat liver cell proliferation.

BACKGROUND: Zinc finger protein 143(ZNF143), a member of the Krüppel C2H2-type zinc finger protein family, is strongly associated with cell cycle regulation and cancer development. A recent study suggested that ZNF143 plays as a transcriptional activator that promotes hepatocellular cancer (HCC) cell proliferation and cell cycle transition. However, the exact biological role of ZNF143 in liver regeneration and normal liver cell proliferation has not yet been investigated. METHODS: In our study, we constructed a stable rat liver cell line (BRL-3A) overexpressing ZNF143 and then integrated RNA-seq and Cleavage Under Targets and Tagmentation (CUT&Tag) data to identify the mechanism underlying differential gene expression. RESULTS: Our results show that ZNF143 expression is upregulated during the proliferation phase of liver regeneration after 2/3 partial hepatectomy (PH). The cell counting kit-8 (CCK-8) assay, EdU staining and RNA-seq data analyses revealed that ZNF143 overexpression (OE) significantly inhibited BRL-3A cell proliferation and cell cycle progression. We then performed CUT&Tag assays and found that approximately 10% of ZNF143-binding sites (BSs) were significantly changed genome-wide by ZNF143 OE. However, CCCTC-binding factor (CTCF) binding to chromatin was not affected. Interestingly, the integration analysis of RNA-seq and CUT&Tag data showed that some of genes affected by ZNF143 differential BSs are in the center of each gene regulation module. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that these genes are critical in the maintenance of cell identity. CONCLUSION: These results indicated that the expression level of ZNF143 in the liver is important for the maintenance of cell identity. ZNF143 plays different roles in HCC and normal liver cells and may be considered as a potential therapeutic target in liver disease.

Changes in Higher-Order Chromosomal Structure of Klebsiella pneumoniae Under Simulated Microgravity.

Our previous work have shown that certain subpopulations of Klebsiella pneumoniae exhibit significant phenotypic changes under simulated microgravity (SMG), including enhanced biofilm formation and cellulose synthesis, which may be evoked by changes in gene expression patterns. It is well known that prokaryotic cells genomic DNA can be hierarchically organized into different higher-order three-dimensional structures, which can highly influence gene expression. It is remain elusive whether phenotypic changes induced by SMG in the subpopulations of K. pneumoniae are driven by genome higher-order structural changes. Here, we investigated the above-mentioned issue using the wild-type (WT) K. pneumoniae (WT was used as a control strain and continuously cultivated for 2 weeks under standard culture conditions of normal gravity) and two previous identified subpopulations (M1 and M2) obtained after 2 weeks of continuous incubation in a SMG device. By the combination of genome-wide chromosome conformation capture (Hi-C), RNA-seq and whole-genome methylation (WGS) analyses, we found that the along with the global chromosome interactions change, the compacting extent of M1, M2 subpopulations were much looser under SMG and even with an increase in active, open chromosome regions. In addition, transcriptome data showed that most differentially expressed genes (DEGs) were upregulated, whereas a few DEGs were downregulated in M1 and M2. The functions of both types DEGs were mainly associated with membrane fractions. Additionally, WGS analysis revealed that methylation levels were lower in M1 and M2. Using combined analysis of multi-omics data, we discovered that most upregulated DEGs were significantly enriched in the boundary regions of the variable chromosomal interaction domains (CIDs), in which genes regulating biofilm formation were mainly located. These results suggest that K. pneumoniae may regulate gene expression patterns through DNA methylation and changes in genome structure, thus resulting in new phenotypes in response to altered gravity.

Triple-Function Au-Ag-Stuffed Nanopancakes for SERS Detection, Discrimination, and Inactivation of Multiple Bacteria.

New strategies combining sensitive pathogenic bacterial detection and high antimicrobial efficacy are urgently desirable. Here, we report smart triple-functional Au-Ag-stuffed nanopancakes (AAS-NPs) exhibiting (1) controllably oxidative Ag-etching thickness for simultaneously obtaining the best surface-enhanced Raman scattering (SERS) enhancement and high Ag-loading antibacterial drug delivery, (2) expressive Ag+-accelerated releasing capability under neutral phosphate-buffered saline (PBS) (pH ∼ 7.4) stimulus and robust antibacterial effectiveness involving sustainable Ag+ release, and (3) three-in-one features combining specific discrimination, sensitive detection, and inactivation of different pathogenic bacteria. Originally, AAS-NPs were synthesized by particle growth of the selective Ag-etched Au@Ag nanoparticles with K3[Fe(CN)6], followed by the formation of an unstable Prussian blue analogue for specifically binding with bacteria through the cyano group. Using specific bacterial "fingerprints" resulting from the introduction of dual-function 4-mercaptophenylboronic acid (4-MPBA, serving as both the SERS tag and internal standard) and a SERS sandwich nanostructure that was made of bacteria/SERS tags/AAS-NPs, three bacteria (E. coli, S. aureus, and P. aeruginosa) were highly sensitively discriminated and detected, with a limit of detection of 7 CFU mL-1. Meanwhile, AAS-NPs killed 99% of 1 × 105 CFU mL-1 bacteria within 60 min under PBS (pH ∼ 7.4) pretreatment. Antibacterial activities of PBS-stimulated AAS-NPs against S. aureus, E. coli, and P. aeruginosa were extraordinarily increased by 64-fold, 72-fold, and 72-fold versus PBS-untreated AAS-NPs, respectively. The multiple functions of PBS-stimulated AAS-NPs were validated by bacterial sensing, inactivation in human blood samples, and bacterial biofilm disruption. Our work exhibits an effective strategy for simultaneous bacterial sensing and inactivation.

Ulinastatin Improves Renal Microcirculation by Protecting Endothelial Cells and Inhibiting Autophagy in a Septic Rat Model.

INTRODUCTION: Increased permeability of the renal capillaries is a common consequence of sepsis-associated acute kidney injury. Vascular endothelial (VE)-cadherin is a strictly endothelial-specific adhesion molecule that can control the permeability of the blood vessel wall. Additionally, autophagy plays an important role in maintaining cell stability. Ulinastatin, a urinary trypsin inhibitor, attenuates the systemic inflammatory response and visceral vasopermeability. However, it is uncertain whether ulinastatin can improve renal microcirculation by acting on the endothelial adhesion junction. METHODS: We observed the effect of ulinastatin in a septic rat model using contrast-enhanced ultrasonography (CEUS) to evaluate the perfusion of the renal cortex and medulla. Male adult Sprague Dawley rats were subjected to cecal ligation and puncture and divided into the sham, sepsis, and ulinastatin groups. Ulinastatin (50,000 U/kg) was injected into the tail vein immediately after the operation. The CEUS was performed to evaluate the renal microcirculation perfusion at 3, 6, 12, and 24 h after the operation. Histological staining was used to evaluate kidney injury scores. Western blot was used to quantify the expression of VE-cadherin, LC3II, and inflammatory factors (interleukin-1ß, interleukin-6, and tumor necrosis factor-α) in kidney tissue, and enzyme-linked immunosorbent assay detected serum inflammatory factors and kidney function and early kidney injury biomarker levels. RESULTS: Compared with the sham group, ulinastatin reduced the inflammatory response, inhibited autophagy, maintained the expression of VE-cadherin, and meliorated cortical and medullary perfusion. CONCLUSION: Ulinastatin effectively protects the adhesion junction and helps ameliorate the perfusion of kidney capillaries during sepsis by the inhibition of autophagy and the expression of inflammatory factors.

[Effect of Xuebijing injection on endothelial microparticles and renal cortical microcirculation in septic rats].

OBJECTIVE: To clarify the characteristics of renal cortical microcirculation and its relationship with the expression of plasma endothelial microparticle (EMP) in septic rats, and to evaluate the effect of Xuebijing injection as an adjuvant therapy of antibiotics on septic AKI. METHODS: The 8-10 weeks old specific pathogen free (SPF) male Sprague-Dawley (SD) rats were divided into sham operation group (Sham group), positive drug control group and Xuebijing group by the random number table method, with 10 rats in each group. The cecal ligation and puncture (CLP) with large ligation (ligated 75% of the cecum) was used to prepare a rat high-grade sepsis model; in the Sham group, the cecum was stretched without ligation or puncture. Due to the high mortality of CLP with large ligation, Xuebijing injection (4 mL/kg, 12 hours per time) and imipenem/cilastatin injection (90 mg/kg, 6 hours per time) were administered to the rats in the Xuebijing group via the tail vein immediately after the model was produced. Normal saline and imipenem/cilastatin were administered to the rats by the same methods in the positive drug control group. The rats in the Sham group were treated with the same volume of normal saline as any of the other two groups at the same frequency. At 48 hours after model reproduction, the mean arterial pressure (MAP) and blood lactic acid (Lac) of the rats were measured. The renal cortical microcirculation was monitored by using side stream dark-field imaging. Renal hypoxia signals were assessed by pimonidazole chloride immunohistochemistry. Plasma EMP levels were determined by using flow cytometry, and then the correlation between EMP and microcirculation parameters of renal cortex was analyzed. At the same time, the serum creatinine (SCr) was measured, and the renal injury score (Paller score) was used to evaluate the severity of renal tissue pathological damage. RESULTS: Compared with the Sham group, perfused vessel density (PVD), microvascular flow index (MFI) and MAP in the positive drug control group and the Xuebijing group decreased significantly, the positive expression of hypoxia probe (pimonidazole) increased, Lac, EMP, Paller score and SCr increased significantly. However, compared with the positive drug control group, the renal cortical microcirculation in the Xuebijing group was improved significantly, PVD and MFI were increased significantly [PVD (mm/mm2): 16.20±1.20 vs. 9.77±1.12, MFI: 2.46±0.05 vs. 1.85±0.15, both P < 0.05], Lac was reduced significantly (mmol/L: 4.81±1.23 vs. 6.08±1.09, P < 0.05), MAP increased slightly [mmHg (1 mmHg = 0.133 kPa): 84.00±2.00 vs. 80.00±2.00, P > 0.05], suggested that Xuebijing injection improved renal microcirculation perfusion in septic rats, and this effect did not depend on the change of MAP. The positive expression of pemonidazole in renal cortex of the Xuebijing group was significantly lower than that of the positive drug control group [(35.89±1.13)% vs. (44.93±1.37) %, P < 0.05], suggested that Xuebijing injection alleviated renal hypoxia. The plasma EMP levels of rats in the Xuebijing group were significantly lower than those in the positive drug control group (×106/L: 3.49±0.17 vs. 5.78±0.22, P < 0.05), and the EMP levels were significantly negatively correlated with PVD and MFI (r values were -0.94 and -0.95, respectively, both P < 0.05), indicated that the increase of plasma EMP was highly correlated with renal microcirculation disorder, and Xuebijing injection inhibited the increase of plasma EMP levels. The Paller score in the Xuebijing group was significantly lower than that in the positive drug control group (46.90±3.84 vs. 62.70±3.05, P < 0.05), and the level of SCr was also significantly lower than that in the positive drug control group (µmol/L: 121.1±12.4 vs. 192.7±23.9, P < 0.05), which suggested that Xuebijing injection relieved kidney injury and improved renal function in septic rats. CONCLUSIONS: As an adjuvant therapy of antibiotics, Xuebijing injection could inhibit the expression of plasma EMP in rats with sepsis, improve renal cortex microcirculation, and reduce kidney injury.

A Dual-Control Strategy by Phosphate Ions and Local Microviscosity for Tracking Adenosine Triphosphate Metabolism in Mitochondria and Cellular Activity Dynamically.

Adenosine triphosphate (ATP) acts as the main energy source for growth and development in organisms, and the disorder reflects the mitochondrial damage to a large extent. Therefore, an efficient tool for the evaluation of the ATP metabolic level is important to track mitochondrial health, providing an additional perspective for an in-depth long-term study on living activities. Herein, a twisted intramolecular charge transfer (TICT) framework is utilized to build up a sensitive receptor, Mito-VP, with a negligible background to target mitochondrial ATP metabolism by monitoring the phosphate ion (Pi) level upon ATP hydrolysis under the overall consideration of the structural and functional features of mitochondria. The responsive fluorescence could be lighted on under the dual control of Pi and local microviscosity, and the two steps of ATP hydrolysis could be captured through fluorescence. In addition to the well-behaved mitochondrial targeting, the energy metabolism at cellular and organism levels has been clarified via mitosis and zebrafish development, respectively.

AND-Logic Strategy for Accurate Analysis of Alzheimer's Disease via Fluorescent Probe Lighted Up by Two Specific Biomarkers.

Alzheimer's disease (AD) has become a global threat to the elderly health with a short survival time after diagnosis. Due to the asymptomatic stage during the early development, patients are usually diagnosed at the middle or late stage. Therefore, an efficient tool for AD early diagnosis deserves considerable attention, which could make a significant contribution to the treatment intervention. A fluorescent probe has been widely applied for detecting and visualizing species of interest in vitro and in vivo, and the proper reaction between the probe and analytes is responsible for the fluorescence change to provide a lighting-on or ratiometric responsive pattern with satisfactory sensing behavior. In this work, we report the first attempt to build up an AND-logic probe P2 for AD accuracy diagnosis taking butyrylcholinesterase (BChE) and reactive oxygen species (ROSs) as dual targets. Upon the co-stimulation by these two factors through enzymatic hydrolysis and redox reaction, the NIR emission could be readily turned on. This AND sensing pattern avoided the false-positive response effectively, and other diseases sharing one biomarker could hardly induce a NIR fluorescence response. The sensing assay has also been confirmed to be feasible in vitro and in vivo with good sensibility and selectivity. It is worth mentioning that the probe structure has been optimized in terms of the linkage length. This study shows that probe P2 with a connecting arm of medium length (one methylene, n = 1) has superior sensing performance, promising to provide a reference for the relative structure design.

Fluorescent detection of microRNA-21 in MCF-7 cells based on multifunctional gold nanorods and the integration of chemotherapy and phototherapy.

MicroRNA-21 is an important biomarker of tumor early prediction and metastasis, and its accurate detection is of great significance for tumor diagnosis and treatment. It will be a meaningful work to combine the detection of RNA with chemotherapy and photothermal therapy on the same composite material. Herein, we designed a multifunctional nanocomposite based on gold nanorods (AuNRs), making use of microRNA-triggered drug release and near-infrared photothermal effect, which has been developed for cancer therapy and microRNA-21detection. Firstly, the AuNRs with photothermal effect were synthesized as carriers for drug delivery. Then the surface of gold nanorods was modified by functional DNA chains to provide an efficient site for doxorubicin (DOX) loading. Finally, folic acid was introduced to achieve the targeted treatment of MCF-7 cells. The microRNA competed with the double-stranded DNA, resulting in the release of DOX and the recovery of fluorescence signal located at 595 nm with an excitation of 488 nm effectively. The nano-biosensor could not only achieve dual-function of diagnosis and treatment of cancer cells, but also accomplish the detection of microRNA in tumor cells. It showed a high selectivity for microRNA-21 determination with a limit of detection (LOD) of 2.1 nM from the linear relationship from 1.0 × 10-5 M to 5.0 × 10-7 M. This scheme provides an outstanding strategy for cell imaging, treatment, and detection, which serves as a promising candidate in the field of biomedical research.

Xuebijing injection in septic rats mitigates kidney injury, reduces cortical microcirculatory disorders, and suppresses activation of local inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Xuebijing injections originate from the traditional Chinese medicine (TCM) prescription XuefuZhuyu Decoction. It is composed of five Chinese herbal extracts; Carthami flos, Paeoniae radix rubra, Chuanxiong rhizoma, Salviae miltiorrhizae, and Angelicae Sinensis radix. The China Food and Drug Administration approved Xuebijing injections as a TCM preparation for the adjuvant treatment of sepsis. AIM OF THE STUDY: This study aims to determine the effects of Xuebijing injections as an adjuvant to antibiotics for the treatment of renal microcirculatory dysfunction and renal inflammation in rats with sepsis. MATERIALS AND METHODS: The rats received a sham operation (Sham), sham operation followed by Xuebijign injection (Sxbj), cecal ligation and puncture (CLP), or CLP followed by Xuebijing injection (Cxbj). Renal microvascular perfusion in the cortex and oxygenation were assessed at different times after sepsis induction. Renal levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and high mobility group box (HMGB)-1 were measured. Urinary TIMP-2 × IGFBP-7 and neutrophil gelatinase-associated lipocalin (NGAL) were measured as kidney biomarkers, and serum creatinine (SCr) was used to assess kidney injury. Tissue samples were stained for histologic evaluation. RESULTS: The induction of sepsis increased local inflammation and decreased renal microvascular perfusion and oxygenation. Compared with the CLP group, the Cxbj group displayed improvements in microvascular perfusion and oxygenation (p < 0.05). The CLP group had significant increases in renal inflammatory biomarkers (IL-1ß, IL-6, TNF-α, and HMGB-1; p < 0.05) and Xuebijing injection reduced the levels of these markers. The levels of urinary TIMP-2 × IGFBP-7, NAGL, and SCr were lower in the Cxbj group than in the CLP group (p < 0.05), and the CLP group had a higher Paller score than the Cxbj group (p < 0.05). However, the CLP and Cxbj groups had no significant difference in mortality. CONCLUSIONS: This study into the early stages of sepsis in a rat model indicated that as an adjuvant therapy to antibiotics, Xuebijing injection improved renal perfusion and oxygenation, suppressed renal inflammation, and ameliorated kidney dysfunction. However, Xuebijing injection had no impact on mortality.

Perfusion microvessel density in the cerebral cortex of septic rats is negatively correlated with endothelial microparticles in circulating plasma.

In sepsis, endothelial microparticles (EMPs) released from endothelial cells (ECs) participate in microcirculation dysfunction through pro-coagulant and pro-inflammatory effects, which can lead to sepsis-associated brain dysfunction. However, the relationship between EMPs and cerebral cortical perfusion microvessel density has not been explored. A closed cranial window was created in rats who were tended to until the cerebral cortex edema caused by preparation of the cranial window subsided, and the microvessel density was stable. A cecal ligation and puncture (CLP) sepsis procedure was then performed on day 6, post-surgery. At 12 and 24 h after the CLP, cerebral cortical perfusion microvessel density was measured with optical coherence tomography angiography (OCTA), followed by measurement of EMPs to evaluate the relationship between these factors. Microvessel density changed from 46.38 % ± 7.65 % on the day of surgery to 35.87 % ± 11.05 % on the second day and 36.71 % ± 11.38 % on the third day after surgery, and then increased daily. The microvessel density decreased to 27.20 % ± 8.50 % 24 h after CLP, which was significantly lower than that immediately and 12 h after CLP (P < 0.001). EMPs increased progressively at 12 and 24 h after CLP. Moreover, there was a negative correlation between EMPs and microvessel density (r=-0.56, P = 0.01). Edema and microvessel density decreased in the local cerebral cortex of the window and then gradually recovered after cranial window surgery. In sepsis, the perfusion microvessel density of the cerebral cortex negatively correlated with the EMPs. Therefore, the perfusion microvessel density can be indirectly evaluated by detecting the plasma EMP level.

Fluorescent Determination of Butyrylcholinesterase Activity and Its Application in Biological Imaging and Pesticide Residue Detection.

Butyrylcholinesterase (BChE) is an essential human cholinesterase relevant to liver conditions and neurodegenerative diseases, which makes it a pivotal biomarker of health. It therefore remains challenging and highly desired to elaborate efficient chemical tools for BChE with simple operations and satisfactory working performance. In this work, a background-free detection strategy was built by virtue of the judicious coupling of a specific BChE-enzymatic reaction and in situ cyclization. High sensitivity with a low limit of detection (LOD) of 0.075 µg/mL could be readily achieved from the blank background and the as-produced emissive indicators, and the specific reaction site contributed to the high selectivity over other bio-species even acetylcholinesterase (AChE). In addition to the multifaceted spectral experiments to verify the sensing mechanism, this work assumed comprehensive studies on the application. The bio-investigation ranged from cells to an organism, declaring a noteworthy prospect in disease diagnosis, especially for Alzheimer's disease (AD), a common neurodegenerative disease with over-expressed BChE. Moreover, its excellent work for inhibition efficacy elucidation was also proved with the accuracy IC50 of tacrine for BChE (8.6 nM), giving rise to an expanded application for trace pesticide determination.

Acute kidney injury in critically ill cirrhotic patients with spontaneous bacterial peritonitis: a comparison of KDIGO and ICA criteria.

INTRODUCTION: Acute kidney injury (AKI) is an important independent predictor of mortality in cirrhotic patients with spontaneous bacterial peritonitis (SBP). However, the definition of AKI in cirrhosis has been debated for many years. This study aims to compare the prediction accuracy of Kidney Disease: Improving Global Outcomes (KDIGO) and International Club of Ascites (ICA) criteria for hospital mortality in cirrhotic patients with SBP admitted to the intensive care unit (ICU). MATERIAL AND METHODS: Two hundred and sixteen cirrhotic patients with SBP consecutively admitted to the ICU during 2010-2017 were retrospectively analyzed. Demographic parameters and clinical variables were collected with case report forms. Risk factors for hospital mortality were identified through a multivariate logistic regression analysis. The predictive value of ICA and KDIGO criteria was analyzed by the area under the receiver operating characteristic curve (AUROC). The primary endpoint was hospital mortality. RESULTS: Overall hospital mortality in our population was 73.6%. Incidence of AKI was 83.8% and 81.5% according to the KDIGO and ICA classifications respectively, associated with increased in-hospital and 180-day mortality. The AKI was an independent risk factor for hospital mortality. The risk factor of AKI according to KDIGO was greater than that of ICA. The AUROC for in-hospital mortality for ICA and KDIGO was 0.730 and 0.752, respectively. However, the predictive ability of ICA criteria for in-hospital mortality was non-inferior to that of KDIGO criteria (p = 0.123). CONCLUSIONS: Both ICA and KDIGO criteria were good tools with excellent prediction performance for hospital mortality in cirrhotic patients with SBP admitted to the ICU.

In situ generated chromophore as the indicator for background-free sensing strategy of hydrazine with high sensitivity with in vitro and in vivo applications.

A chromophore is essential to a classic molecular probe, but its intrinsic optical properties can trigger a spectral background, which is considered to produce a negative influence on detection sensitivity. Hence, developing spectral sensing assays with chromophores generated in situ by probes and analytes could realize detection. Herein, we elaborated a novel proposal based on the in situ condensation reaction between 4-diethylaminobenzaldehyde (DEASA) and hydrazine readily promoted by CTAB micelles, resulting in new chromophores with intramolecular hydrogen bonds generated in situ acting as indicators for hydrazine. A background-free detection pattern was, therefore, formulated, along with a relatively low detection limit of 0.42 nM. This avoided tedious preparation and the use of organic solvents during the experiments. In addition, extensive studies, including actual water/serum samples, living cells, and even mouse imaging, revealed that the DEASA probe and the well-designed in situ sensing scheme exhibited good performance regarding future applications in terms of sensitivity, anti-interference capability, and imaging stability.

Twisted intramolecular charge transfer (TICT) based fluorescent probe for lighting up serum albumin with high sensitivity in physiological conditions.

Accurate detection of human serum albumin (HSA) in biological samples is quite meaningful for early disease diagnosis and treatment. Herein, a novel fluorescent probe 1-ethyl-4-[2-[4-(diethylamino)-2-hydroxyphenyl]ethenyl]]-pyridinium salt (DEHP) was developed for HSA determination. The inherent fluorescence of DEHP is essentially negligible at physiological conditions assigned to the well-developed twisted intramolecular charge transfer (TICT) protocol. An intriguing fluorescence light up is triggered as the addition of HSA, on account of the inhibited TICT procedure when DEHP enters the hydrophobic cavity of protein HSA. This combination leads to a turn on fluorescent response for HSA with a detection limit of 4.8 nM. After an overall investigation, it has been proved that the strong binding between DEHP and HSA is specific-site-related. In additional, the probe implies a great potential to assist clinical diagnosis due to the usage in actual serum detection. Cell imaging also shows that the probe is expected to monitor HSA production process at cell level.

Correction: Antimicrobial peptide based magnetic recognition elements and Au@Ag-GO SERS tags with stable internal standards: a three in one biosensor for isolation, discrimination and killing of multiple bacteria in whole blood.

[This corrects the article DOI: 10.1039/C8SC04637A.].